1. Field of Invention
The present invention relates to magnetic resonance identity systems, magnetic resonance imaging contrast agents and spectroscopic agents, and magnetic microstructures for magnetic resonance systems and methods of production.
2. Discussion of Related Art
Magnetic resonance imaging (Lauterbur, P. C. Image formation by induced local interactions: examples employing nuclear magnetic resonance. Nature 242, 190-191 (1973); Mansfield, P. & Grannell P. K. NMR ‘diffraction’ in solids? J. Phys. C 6, L422-L426 (1973)) (MRI) has become an invaluable, widely used medical diagnostic and research tool (Callaghan, P. T. Principles of nuclear magnetic resonance microscopy. (Oxford Univ. Press, New York, 1991)). Nevertheless, despite numerous chemically-synthesized image-enhancing agents (Nelson, K. L. & Runge, V. M. Basic principles of MR contrast. Topics in Magn. Reson. Imaging 7, 124-136 (1995); Runge, V. M. & Wells, J. W. Update: safety, new applications, new MR agents. Topics in Magn. Reson. Imaging 7, 181-195 (1995); Weissleder, R. et al. Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. Radiology 175, 489-493 (1990); Woods, M., Woessner, D. E. & Sherry, A. D. Paramagnetic lanthanide complexes as PARACEST agents for medical imaging. Chem. Soc. Rev. 35, 500-511 (2006); Lanza, G. M. et al. 1H/19F magnetic resonance molecular imaging with perfluorocarbon nanoparticles. Current Topics in Devel. Bio. 70, 57-76 (2005)), MRI still lacks the sensitivity and the multiplexing capabilities of optical imaging that benefits from colored fluorophores (Mason, W. T. (ed) Fluorescent and Luminescent Probes for Biological Activity. (Academic Press, London, 1999)), multi-spectral quantum dots (Bruchez, M. Jr., Moronne, M., Gin, P., Weiss, S. & Alivisatos, A. P. Semiconductor nanocrystals as fluorescent biological labels. Science 281, 2013-2016 (1998); Chan, W. C. W. & Nie, S. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281, 2016-2018 (1998); Alivisatos, P. The use of nanocrystals in biological detection. Nat. Biotechnol. 22, 47-52 (2004)), and microfabricated barcodes (Nicewarner-Peria, S. R. et al. Submicrometer metallic barcodes. Science 294, 137-141 (2001)), for multi-functional encoding and biomolecular/cellular labeling.
Being able to distinguish with MRI between different types of cells, at the single cell level, would profoundly impact cellular biology and early disease detection and diagnosis. Currently, MRI cell tracking employs the magnetically dephased signal from the water surrounding cells labeled with many superparamagnetic iron oxide nanoparticles (Weissleder, R. et al. Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. Radiology 175, 489-493 (1990); Dodd, S. J. et al. Detection of single mammalian cells by high-resolution magnetic resonance imaging. Biophys. J. 76, 103-109 (1999); Cunningham, C. H. et al. Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles. Magn. Reson. Med. 53, 999-1005 (2005)) (SPIOs) or dendrimers (Bulte, J. W. M. et al. Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat. Biotechnol. 19, 1141-1147 (2001)), or individual micrometer-sized iron oxide particles (Hinds, K. A. et al. Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells. Blood. 102, 867-872 (2003); Shapiro, E. M., Skrtic, S. & Koretsky, A. P. Sizing it up: cellular MRI using micron-sized iron oxide particles. Magn. Reson. Med. 53, 329-338 (2005)) (MPIOs) that benefit from increased robustness and immunity to label dilution via cell division. However, the continuous spatial decay of the external fields surrounding these, or any other, magnetizable particles imposes a continuous range of Larmor frequencies that broadens the water line, obscuring distinction between possible different types of magnetic particles that might specifically label different types of cells. Their utility would be greatly enhanced if they could instead frequency shift the water by discrete controllable amounts, transforming a monochrome/binary contrasting agent (magnetically labeled or not) into a “colored” spectral set of distinguishable tags. There is thus a need for improved magnetic resonance imaging contrast agents.